Fracture Healing Can Be Accelerated by a Combination of Two Drugs

A combination of two drugs, already approved and used for other indications, can stimulate the release of a special type of stem cells from the bone marrow that have regenerative potential, thereby accelerating the healing of broken bones. These are the conclusions of a recent study, the results of which were presented in the journal npj Regenerative Medicine. Although the concept has only been confirmed in animals so far, researchers hope that further clinical trials will proceed quickly, given that the safety of both drugs for humans has already been proven.
"Our body is constantly repairing itself," says the senior author of the study, Sarah Rankin. "In recent decades, evidence has emerged that physiological renewal and tissue regeneration occur thanks to stem cells. This also applies to bone tissue: when a bone breaks, stem cells are activated for its healing. However, the capabilities of our body are not limitless, and when it comes to truly serious injuries, it is not always able to cope on its own."

A large number of modern studies focus on the treatment with mesenchymal stem cells (MSCs). This is the most important population of stem cells in the adult body. They were first discovered and isolated from the stroma of bone marrow. The value of MSCs lies in their ability to transform into various types of mature cells, including bone, cartilage, fat, nerve, and muscle cells. These cells have special immunomodulatory abilities and participate in recovery processes.
Many treatment methods using mesenchymal stem cells that are currently in development involve extracting a small number from source tissues, such as the patient's bone marrow, subsequently growing them in laboratory conditions, and reintroducing them. In the new study, researchers sought to determine whether any of the already approved drugs could stimulate the body's natural ability to release MSCs for faster fracture healing. They tested the effectiveness of a combination of two already used medications on rodents with spinal injuries.

The first of the two drugs in question is plerixafor – an antitumor drug prescribed to patients with non-Hodgkin lymphoma and multiple myeloma. It is an immunostimulator used to mobilize hematopoietic stem cells from the bone marrow into the bloodstream. The second is a beta3-adrenergic agonist, which is used as an aid in controlling bladder function.
Experiments showed that this combination of drugs mobilizes mesenchymal stem cells into the bloodstream and accelerates the process of bone formation and healing by enhancing calcium binding at the site of injury. In the next phase of research, scientists want to test whether these results can be confirmed in humans.

"First, we need to determine whether these drugs promote the release of stem cells in healthy volunteers, and only after that can we test the experimental combination on people with fractures," says Sarah Rankin. "These drugs have long been approved by the FDA, and we are confident in their safety. The only thing we need is funding for clinical trials in humans."
The authors note that previous studies have identified an increase in the volume of circulating MSCs in the blood after injuries such as burns, bone fractures, and even heart attacks. Their hypothesis is that the release of these cells is a physiological process that contributes to overall regeneration after injury, and if the number of circulating MSCs can be increased pharmacologically, it will help accelerate the recovery of various types of tissues.

Researchers emphasize that the current study only examined the increase in the number of circulating mesenchymal stem cells and the speed of healing spinal injuries compared to the absence of drug treatment. The results obtained do not provide any information about the effect of the studied combination of drugs on nerve healing or the restoration of mobility.
Therefore, to objectively assess the clinical significance of these results, a series of additional studies and experiments is necessary. Nevertheless, the authors note that repurposing existing drugs to enhance stem cell activity is a simpler, cheaper, and more effective way to accelerate healing compared to other, more complex and time-consuming stem cell treatment methods currently in development.

"Instead of developing new stem cell treatment techniques from scratch, which involve lengthy and costly trials, our approach utilizes the potential of the body's own stem cells, which we enhance with existing drugs," says Sarah Rankin. "We already know that the drugs used in our proposed combination are safe, and now we just need to find out if they truly help our body recover."